26 research outputs found
Performing and Processing FNA of Anterior Fat Pad for Amyloid
Historically, heart, liver, and kidney biopsies were performed to demonstrate amyloid deposits in amyloidosis. Since the clinical presentation of this disease is so variable and non-specific, the associated risks of these biopsies are too great for the diagnostic yield. Other sites that have a lower biopsy risk, such as skin or gingival, are also relatively invasive and expensive. In addition, these biopsies may not always have sufficient amyloid deposits to establish a diagnosis. Fat pad aspiration has demonstrated good clinical correlation with low cost and minimal morbidity. However, there are no standardized protocols for performing this procedure or processing the aspirated specimen, which leads to variable and nonreproducible results. The most frequently utilized modality for detecting amyloid in tissue is an apple-green birefringence on Congo red stained sections using a polarizing microscope. This technique requires cell block preparation of aspirated material. Unfortunately, patients presenting in early stage of amyloidosis have minimal amounts of amyloid which greatly reduces the sensitivity of Congo red stained cell block sections of fat pad aspirates. Therefore, ultrastructural evaluation of fat pad aspirates by electron microscopy should be utilized, given its increased sensitivity for amyloid detection. This article demonstrates a simple and reproducible procedure for performing anterior fat pad aspiration for the detection of amyloid utilizing both Congo red staining of cell block sections and electron microscopy for ultrastructural identification
A single center phase II study of ixazomib in patients with relapsed or refractory cutaneous or peripheral Tâcell lymphomas
The transcription factor GATAâ3, highly expressed in many cutaneous Tâcell lymphoma (CTCL) and peripheral Tâcell lymphomas (PTCL), confers resistance to chemotherapy in a cellâautonomous manner. As GATAâ3 is transcriptionally regulated by NFâÎșB, we sought to determine the extent to which proteasomal inhibition impairs NFâÎșB activation and GATAâ3 expression and cell viability in malignant T cells. Proteasome inhibition, NFâÎșB activity, GATAâ3 expression, and cell viability were examined in patientâderived cell lines and primary Tâcell lymphoma specimens ex vivo treated with the oral proteasome inhibitor ixazomib. Significant reductions in cell viability, NFâÎșB activation, and GATAâ3 expression were observed preclinically in ixazomibâtreated cells. Therefore, an investigatorâinitiated, singleâcenter, phase II study with this agent in patients with relapsed/refractory CTCL/PTCL was conducted. Concordant with our preclinical observations, a significant reduction in NFâÎșB activation and GATAâ3 expression was observed in an exceptional responder following one month of treatment with ixazomib. While ixazomib had limited activity in this small and heterogeneous cohort of patients, inhibition of the NFâÎșB/GATAâ3 axis in a single exceptional responder suggests that ixazomib may have utility in appropriately selected patients or in combination with other agents.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139920/1/ajh24895.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139920/2/ajh24895_am.pd
Investigating Safety And Preliminary Efficacy Of Afm13 Plus Pembrolizumab In Patients With Relapsed/Refractory Hodgkin Lymphoma After Brentuximab Vedotin Failure
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149522/1/hon134_2629.pd
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A phase 1b study of AFM13 in combination with pembrolizumab in patients with relapsed or refractory Hodgkin lymphoma
In relapsed/refractory Hodgkin lymphoma (R/R HL), immunotherapies such as the anti-programmed death-1 inhibitor pembrolizumab have demonstrated efficacy as monotherapy and are playing an increasingly prominent role in treatment. The CD30/CD16A-bispecific antibody AFM13 is an innate immune cell engager, a first-in-class, tetravalent antibody, designed to create a bridge between CD30 on HL cells and the CD16A receptor on natural killer cells and macrophages, to induce tumor cell killing. Early studies of AFM13 have demonstrated signs of efficacy as monotherapy for patients with R/RHL and the combination of AFM13 with pembrolizumab represents a rational new treatment modality. Here, we describe a phase 1b, dose-escalation study to assess the safety and preliminary efficacy of AFM13 in combination with pembrolizumab in patients with R/R HL. The primary objective was estimating the maximum tolerated dose; the secondary objectives were to assess safety, tolerability, antitumor efficacy, pharmacokinetics, and pharmacodynamics. In this heavily pretreated patient population, treatment with the combination of AFM13 and pembrolizumab was generally well tolerated, with similar safety profiles compared to the known profiles of each agent alone. The combination of AFM13 with pembrolizumab demonstrated an objective response rate of 88% at the highest treatment dose, with an 83% overall response rate for the overall population. Pharmacokinetic assessment of AFM13 in the combination setting revealed a half-life of up to 20.6 hours. This proof-of-concept study holds promise as a novel immunotherapy combination worthy of further investigation
Time Trends in the Incidence and Treatment of Extra-Abdominal and Abdominal Aggressive Fibromatosis: A Population-Based Study
BACKGROUND: Aggressive fibromatosis (AF) is a locally infiltrating soft-tissue tumor. In a population-based study in the Netherlands, we evaluated time trends for the incidence and treatment of AF. METHODS: In PALGA: Dutch Pathology Registry, all patients diagnosed between 1993 and 2013 as having extra-abdominal or abdominal wall aggressive fibromatosis were identified and available pathology data of the patients were evaluated. Epidemiological and treatment-related factors were analyzed with Ï(2)and regression analysis. RESULTS: During the study period, 1134 patients were identified. The incidence increased from 2.10 to 5.36 per million people per year. Median age at the time of diagnosis increased annually by B 0.285 (PÂ =Â 0.001). Female gender prevailed and increased over time [annual odds ratio (OR) 1.022; PÂ =Â 0.058]. All anatomic localizations, but in particular truncal tumors, became more frequent. During the study period diagnostic histological biopsies were performed more often (annual OR 1.096; PÂ <Â 0.001). The proportion of patients who underwent surgical treatment decreased (annual OR 0.928; PÂ <Â 0.001). When resection was preceded by biopsy, 49.8Â % of the patients had R0-resection versus 30.7Â % in patients without biopsy (PÂ <Â 0.001). CONCLUSIONS: In this population-based study, an increasing incidence of extra-abdominal and abdominal-wall aggressive fibromatosis was observed. The workup of patients improved and a trend towards a nonsurgical treatment policy was observed
E-Selectin Inhibition Mitigates Splenic HSC Activation and Myelopoiesis in Hypercholesterolemic Mice With Myocardial Infarction
Myeloma (MM) after autologous transplant (AutoHCT): Biochemical versus clinical progression.
The Combination Of Venetoclax, Lenalidomide And Rituximab In Patients With Newly Diagnosed Mantle Cell Lymphoma Induces High Response Rates And Mrd Undetectability
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/168327/1/hon61_2879.pd